Investigation of synergistic cytotoxic effects of bortezomib and ellagic acid, ferulic acid, caffeic acid combinations on Caco-2, A549 and 3T3 cells

There is growing interest in research using many phenolic acids due to their antioxidant effects for the prevention and treatment of cancer. The data presented in many studies have shown that phenolic acids can play important role in reducing cell viability, modulating the cell cycle and controlling tumor progression by induction of apoptosis. Although bortezomib, one of the proteosome inhibitors, has specific effect for multiple myeloma, there are various studies that it is also effective in many types of cancer. In this thesis, it is aimed to determine the synergistic cytotoxic effects of bortezomib on A549, Caco-2 and 3T3 cell lines in combination with ellagic acid, ferulic acid and caffeic acid. The cytotoxic effects of bortezomib, ellagic acid, ferulic acid and caffeic acid in some concentrations in Caco-2, A549 and 3T3 cells were investigated by MTT method and CDI values were calculated. As a result, it was determined that the combinations of bortezomib and phenolic acids significantly decreased cell viability on Caco-2 and A549 cells in the concentration range of 3.125-25 µM. Bortezomib + ferulic acid and bortezomib + caffeic acid combinations showed important cytotoxic effect on 3T3 cells. According to the results of the CDI ,in the 3.125 µM the combination of bortezomib and caffeic acid showed strong synergistic effect on Caco-2 cells, while bortezomib and ferulic acid, bortezomib and caffeic acid at the same concentration showed strong synergistic effect on 3T3 cells.